Work on this project deals with the mechanism of action of three families of enzymes (1) proteolytic enzymes (pepsin and serine proteases), (2) enzymes that require coenzyme B12 (propanediol dehydratase and methionine synthetase), (3) hydratases (fumarase and aconitase). The principal experimental techniques utilized are, use of fluorine containing substrate analogues, nuclear magnetic resonance and secondary isotope effects.